Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzi-You 1st Road, Sanmin Dist., Kaohsiung City 80708, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Europace. 2023 Dec 28;26(1). doi: 10.1093/europace/euae004.
Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS.
Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023).
Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.
代谢综合征（MetS）与心律失常和心血管死亡率有关。MetS 中心律失常的发生源于心房结构和电重构。小电导钙激活钾电流（SK）调节心房复极，并可能影响心房致心律失常性。本研究通过高脂肪饮食（HFD）模拟 MetS 来研究 SK 电流的调节。
30 只小鼠分为两组，分别用正常饲料（CTL）和 HFD 喂养 4 个月。心电图和超声心动图用于检测心脏电和结构重构。Langendorff 灌流心脏的光学标测用于测量心房动作电位时程（APD）和钙瞬变时程（CaTD）。用爆发性起搏评估心房颤动（AF）的易感性和持续时间。原代分离的心房肌细胞进行全细胞膜片钳用于测量 SK 电流密度。HFD 组心房肌细胞的 SK 电流密度高于 CTL 组（P≤0.037）。HFD 组 SK 通道的 RNA 和蛋白表达增加（P≤0.041 和 P≤0.011）。与 CTL 相比，HFD 中的动作电位时程缩短（P≤0.015）。HFD 中 SK 通道阻滞剂 100 nM 蜂毒肽的应用逆转了心房 APD 的缩短（P≤0.043）。与 CTL 相比，HFD 中的 CaTD 更大（P≤0.029）。HFD 中的钙瞬变衰减（Tau）明显高于 CTL（P=0.001）。HFD 中的 APD 和 CaTD 交替阈值均较高（P≤0.043），同时 HFD 中的 AF 易感性和持续时间较长（P≤0.023）。
apamin 敏感的 SK 电流的上调在 HFD 小鼠的心房致心律失常性中起部分作用。
